1. Field of the Invention
The present invention relates to a novel cancer therapeutic agent and a method for screening for the same. More particularly, the present invention relates to a novel cancer therapeutic agent capable of interfering with the up-regulation of fascin-1 by galectin-3 or the interaction between galectin-3 and GSK-3β, and a method for screening for the same.
2. Description of the Related Art
Cancer is one of the most common causes of morbidity and mortality all over the world today. The incidence of cancer is expected to increase due to the increasing average life expectancy, with the onset age being lowered. The ACS's (American Cancer Society) annual Cancer Statistics article states that in 2007, 12 million or more new cancer cases were diagnosed worldwide, with a death toll of about 7.6 million cancer patients which is a fatality rate of about twenty thousand per day.
In South Korea, cancer (malignant neoplasm) is responsible for the death of 62,887 persons per, which corresponds to 25.5% (29.6% for men and 20.5% for women) of the total death toll of 246,515 persons (death rate 512 per hundred thousands of the population) in 2002, ranking it first amongst the causes of death. Lung cancer, breast cancer, hepatic cancer, colorectal cancer, and pancreatic cancer are in decreasing order the cancer with the highest mortality, accounting for around 70% of total cancer deaths. Lung cancer, gastric cancer, hepatic cancer and colorectal cancer are the leading causes of cancer death in males, accounting for 28,147 deaths in that period (around 70% of all cancer deaths (40,177)). For women, 13,630 deaths, which were around 60% of the total cancer deaths in that period (22,710), were caused by the five cancers of gastric cancer, lung cancer, hepatic cancer, colon cancer and pancreatic cancer.
An analysis report has it that the death rate from gastric cancer has gradually decreased from 24% to 16% over the 10 years between 1996 and 2006.
Although decreasing, the death rate of gastric cancer is significant, and gastric cancer still remains as one of the three leading cancers in South Korea.
When affected by gastric cancer, patients feel a variety of symptoms ranging from no pain to extremely severe pain. In addition, the symptoms of gastric cancer are not peculiar, but resemble general gastrointestinal symptoms. In fact, most patients in the early stage of gastric cancer live without feeling any symptoms. If any, the symptoms of early gastric cancer are so insignificant that they are likely to be neglected by most patients, which contributes to an increase in the mortality rate of gastric cancer.
The best therapy for gastric cancer which has been identified thus far is gastrectomy. That is, the resection of the lesion is the only way to completely heal gastric cancer. Many operative processes may be provided for gastrectomy. Once it has been determined that a surgery would be able to completely heal gastric cancer, a surgical operation is preferably performed wherein as wide a region as possible including the lesion is resected. However, the resection area must be limited in consideration of the sequela of the resection. If the target of the gastrectomy includes neighboring organs such as lymph glands, satisfactory convalescence may be not given to the patients. Upon the metastasis of gastric cancer to other organs, a surgical operation is not a therapy that can offer complete healing. In this regard, alternative therapies such as chemotherapy are taken. Most of the currently used anticancer agents are useful, but temporally, for relieving symptoms or restraining post-operative recurrence and extending the duration of life. However, the administration of anticancer agents imparts the patients with the dual burdens of side effects and financial loss. Therefore, there is a desperate need for a novel cancer therapeutic agent and a method for developing the same.
In association with the progress of gastric cancer, galectins vary in expression level with progression into malignant or benign tumors. Galectins are specific carbohydrate-binding proteins which are widely distributed in humans and animals. Despite having obtained knowledge about the biochemical and microbiological properties of galetins, the exact functions thereof remain controversial. Starting from galectin-1, the members of the galectin family exist as monomers or dimers with molecular weights of 14-36 kDa. Galetin-1, -2, -3, -7 and -8 are known to be involved in the regulation of fetal development and cell growth, attachment and tumorigenesis. Some of the galectin members are distributed primarily on specific organs or cells: galectin-2 is confined specifically to hepatic cancer cells, galectin-4 to the epithelial cells of the gastrointestinal tract, galectin-5 to erythrocytes, and galectin-7 to keratinocytes of the squamous epithelium.
Galectin-3, one of the most studied members of the galectin family, also called CBP-35, Mac-2, εBP, RL-29, L-35 or L-31, having a molecular weight of 26,200-32,300, is implicated in the growth, differentiation and tumorigenesis of cells, fetal development and IgE-mediated allergic responses, and plays an important role in intercellular or cell-matrix binding. Also, galectin-3 is distributed over a wide range of cells including leukocytes, dendritic cells of lymphatic organs, Langerhan's cells, and the epithelial cells of the intestinal mucosa and renal tubules. Particularly, galectin-3 is barely detected in the intestinal crypt epithelium, but increases in expression level with the progression of cell differentiation, suggesting that galectin-3 plays a role in cell development and differentiation. New members of the galectin family continue to be found and 9 have been found thus far. In addition, galectins have in common with interleukin-1 or fibroblast growth factors the fact that they lack signal sequences during expression although they are extracellular proteins.
In contrast to general soluble proteins, galectin-3 can be extracellularly secreted without signal peptides (Woo, H. J., Secretion of macrophage differentiation antigen, Mac-2, 15: 61-68, 1993). It has been anticipated that the analysis of the mechanism of galectin functions at molecular levels would provides a basis for the diagnosis, prevention and treatment of inflammatory diseases such as cancer and arthritis. In fact, a research report states that the expression of galectin-3 is correlated with the generation of carcinoma. However, no reports have disclosed that cancer or inflammatory diseases can be treated by suppressing the expression of galectin-3. Further, nowhere has the mechanism of galectin-3 been reported in previous documents.